Human endonuclease V is a ribonuclease specific for inosine-containing RNA.

Human endonuclease V is a ribonuclease specific for inosine-containing RNA.
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DOI:
10.1038/ncomms3273
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发表时间:
2013
影响因子:
16.6
通讯作者:
Kuraoka, Isao
Kuraoka, Isao
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Morita, Yoko;Shibutani, Toshihiro;Nakanishi, Nozomi;Nishikura, Kazuko;Iwai, Shigenori;Kuraoka, Isao

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脱氧核糖核酸碱基脱胺可以产生误义突变,使人类易患癌症,并干扰其他基本的分子遗传过程;这种脱氨作用由脱氧腺苷产生脱氧肌苷。在大肠杆菌中,高度保守的内切酶V参与了从DNA中去除脱氧肌苷的选择性切除修复。然而,它在人体中的确切活动和作用尚不清楚。在这里,我们将FLJ35220蛋白(大肠杆菌内切酶V, hEndoV的人类同源物)定性为一种针对含肌苷RNA的核糖核酸酶。hEndoV优先与RNA结合,并有效水解位于dsRNA中未配对的含肌苷的ssRNA区域中位于肌苷3 '的第二磷酸二酯键。它定位于细胞的细胞质。核糖核酸酶活性由Tudor葡萄球菌核酸酶促进,并在由腺苷脱氨酶作用于RNA产生的含肌苷的dsRNA上检测。这些结果表明,hEndoV控制着人体内含肌苷RNA的命运。在大肠杆菌中,高度保守的酶内切酶V在DNA修复中起作用。本文作者表明,人核酸内切酶V是一种肌苷3'核糖核酸内切酶,Tudor葡萄球菌核酸酶增强了这种活性,表明人核酸内切酶V在RNA代谢中起作用。
Deamination of DNA bases can create missense mutations predisposing humans to cancer and also interfere with other basic molecular genetic processes; this deamination generates deoxyinosine from deoxyadenosine. In Escherichia coli, the highly conserved endonuclease V is involved in alternative excision repair that removes deoxyinosine from DNA. However, its exact activities and roles in humans are unknown. Here we characterize the FLJ35220 protein, the human homologue of E. coli endonuclease V, hEndoV as a ribonuclease specific for inosine-containing RNA. hEndoV preferentially binds to RNA and efficiently hydrolyses the second phosphodiester bond located 3′ to the inosine in unpaired inosine-containing ssRNA regions in dsRNA. It localizes to the cytoplasm in cells. The ribonuclease activity is promoted by Tudor staphylococcal nuclease and detected on inosine-containing dsRNA created by the action of adenosine deaminases acting on RNA. These results demonstrate that hEndoV controls the fate of inosine-containing RNA in humans. In Escherichia coli, the highly conserved enzyme endonuclease V has a role in DNA repair. Here the authors show that human endonuclease V is an inosine 3' endoribonuclease and that Tudor Staphylococcal nuclease enhances this activity, suggesting a role for human endonuclease V in RNA metabolism.
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